Death Following a Skiing Incident: Severe Exsanguination Due to Rupture of the Left Renal Artery.

With the growing popularity of winter sports, it is necessary to pay more attention to the types of traumatic injuries that a person can sustain in various incidents related to their practice. We present a case in which an adult man died as a result of a collision with a tree while skiing. Although the deaths are associated with different types and severity of craniocerebral injuries in the majority of the cases, here we are dealing with an abdominal injury with rupture of the stomach, pancreas, and left renal artery. The exact localization of the resulting traumatic injuries and the mechanism of their occurrence were examined. Both macroscopic autopsy findings (gross pathology) and histologically proven ones are presented and described. Presenting this case, we want to raise awareness of the different types of injuries received while skiing, as well as to emphasize the possibility of death in the absence of visible external injuries over the victim's body.

Mixed Eccrine Cutaneous Tumor with Folliculo-Sebaceous Differentiation: Case Report and Literature Review.

Background/Introduction: Cutaneous mixed tumor is a rare benign neoplasm that exhibits a wide range of metaplastic changes and differentiation in the epithelial, myoepithelial, and stromal components, which is often confused with various other skin lesions. Case report: We present an unusual case of a 58-year-old woman with a mixed tumor of the upper lip, previously misdiagnosed as adnexal carcinoma on a preoperative biopsy. The excision biopsy shows a well-circumscribed lesion composed of various cells and structures featuring folliculo-sebaceous differentiation embedded in a prominent chondromyxoid stroma. The immunohistochemical study proves the various lineages of differentiation and classifies the neoplasm as the less common eccrine subtype of cutaneous mixed tumor. Discussion: The common embryologic origin of the folliculo-sebaceous apocrine complex leads to a great histological variety of cellular components of mixed tumors and the formation of structures that resemble established types of adnexal neoplasms, which could be a diagnostic pitfall, especially on a small incision biopsy.

Advancing Immunization Coverage and Equity: A Structured Synthesis of Pro-Equity Strategies in 61 Gavi-Supported Countries.

BACKGROUND: Global immunization inequities persist, reflected in the 25 million underimmunized and 18 million zero-dose children in 2021. To identify country approaches to reach underimmunized and zero-dose children, we undertook a structured synthesis of pro-equity strategies across 61 countries receiving programmatic support from Gavi, the Vaccine Alliance. METHODS: We extracted data from 174 Country Joint Appraisals and Multi-Stakeholder Dialogue reports (2016-2020). We identified strategies via a targeted keyword search, informed by a determinants of immunization coverage framework. Strategies were synthesized into themes consolidated from UNICEF's Journey to Health and Immunization (JTHI) and the Global Routine Immunization Strategies and Practices (GRISP) frameworks. RESULTS: We found 607 unique strategies across 61 countries and 24 themes. Strategies to improve care at the point of service (44%); to improve knowledge, awareness and beliefs (25%); and to address preparation, cost and effort barriers (13%) were common. Fewer strategies targeted experience of care (8%), intent, (7%) and after-service (3%). We also identified strategies addressing gender-related barriers to immunization and targeting specific types of communities. CONCLUSIONS: We summarize the range of pro-equity immunization strategies employed in Gavi-supported countries and interpret them thematically. Findings are incorporated into a searchable database which can be used to inform equity-driven immunization programs, policies and decision-making which target underimmunized and zero-dose communities.

Genomic prediction of morphometric and colorimetric traits in Solanaceous fruits.

Selection of high-performance lines with respect to traits of interest is a key step in plant breeding. Genomic prediction allows to determine the genomic estimated breeding values of unseen lines for trait of interest using genetic markers, e.g. single-nucleotide polymorphisms (SNPs), and machine learning approaches, which can therefore shorten breeding cycles, referring to genomic selection (GS). Here, we applied GS approaches in two populations of Solanaceous crops, i.e. tomato and pepper, to predict morphometric and colorimetric traits. The traits were measured by using scoring-based conventional descriptors (CDs) as well as by Tomato Analyzer (TA) tool using the longitudinally and latitudinally cut fruit images. The GS performance was assessed in cross-validations of classification-based and regression-based machine learning models for CD and TA traits, respectively. The results showed the usage of TA traits and tag SNPs provide a powerful combination to predict morphology and color-related traits of Solanaceous fruits. The highest predictability of 0.89 was achieved for fruit width in pepper, with an average predictability of 0.69 over all traits. The multi-trait GS models are of slightly better predictability than single-trait models for some colorimetric traits in pepper. While model validation performs poorly on wild tomato accessions, the usage as many as one accession per wild species in the training set can increase the transferability of models to unseen populations for some traits (e.g. fruit shape for which predictability in unseen scenario increased from zero to 0.6). Overall, GS approaches can assist the selection of high-performance Solanaceous fruits in crop breeding.

First report of Cucurbit aphid-borne yellows virus causing yellowing disease on pumpkin (Cucurbita pepo) and cucumber (Cucumis sativus) in Bulgaria.

Cucurbit aphid-borne yellows virus (CABYV) was first reported in France in 1992 but has since been observed worldwide (Lecoq et al. 1992; Choi and Choi 2016; Buzkan et al. 2017; Zindovic et al. 2017; Vidal et al. 2018; Khanal and Ali, 2018). This virus has caused severe losses to different crops especially to the members of Cucurbitaceae and yield losses can reach up to 40-50% if infection occurs at early stages (Lecoq et al. 1992). In July 2017, leaf samples showing virus-like symptoms were collected from five pumpkin (Cucurbita pepo L. var. Clypeata Alefield) and two cucumber (Cucumis sativus L. cv. Azuma matsunari) plants, growing in а field near Sadovo, Bulgaria. Nearly all plants in the field were affected and displayed green or yellow mosaic, interveinal yellowing, blisters, and leaf deformation (Fig. 1). The collected samples were all symptomatic and were subjected to double antibody sandwich (DAS) or triple antibody sandwich (TAS) enzyme-linked immunosorbent assay (ELISA) to determine the viral agent(s). Specific monoclonal antibodies (Leibniz institute DSMZ, Germany) raised against Cucumber leaf spot virus, Cucurbit chlorotic yellows virus, Cucurbit yellow stunting disorder virus, Cucumber mosaic virus (CMV), Melon necrotic spot virus, Beet western yellows virus (BWYV), CABYV, Watermelon mosaic virus (WMV), Zucchini yellow mosaic virus (ZYMV), and Cucumber green mottle mosaic virus, were used. The total number of tested samples was seven (n=5 from pumpkin and n=2 from cucumber). All of them displayed positive signals for CABYV and BWYV, both belonging to genus Polerovirus, family Luteoviridae. In addition, ZYMV and/or WMV were detected in pumpkins while CMV and/or WMV were detected in cucumber samples, respectively. To confirm the presence of CABYV and/or BWYV, total RNA was isolated from all seven samples by TRI Reagent® (Sigma, St. Louis, USA) and converted to cDNA with First Strand cDNA Synthesis Kit, Thermo Scientific™. Reverse transcription (RT)-polyemerase chain reaction (PCR) was performed using two pairs of primers (CABYV1FW: 5'-TTATCAGGGGACTATGTTTA-3' and CABYV14REV: 5'-GAGGGGATTTTAACTGACTG-3', and BWYV1FW: 5'-AGTAAGTCCTCCCCAACTGA-3' and BWYV2REV: 5'-CTACCCACGACCGTATTCAT-3'), specifically designed to detect CABYV and BWYV, respectively. Amplicons with expected sizes of 1,930 bp were obtained only with CABYV primers for all samples while no fragments were amplified with BWYV primers. The obtained products from two samples (pumpkin and cucumber) were purified and sent to Macrogen Inc., South Korea, for direct sequencing in both directions. High quality nucleotide sequences were submitted to GenBank We have evaluated the quality of the sequencing and trimmed those parts that did not comply the needed quality. The obtained smaller fragments Nucleotide sequences were submitted to GenBank with accession numbers MK671010 (656 bp) and MK671014 (712bp). These sequences contained ORFs encoding CABYV P1-P2 fusion proteins as determined by Blastp analysis (https://blast.ncbi.nlm.nih.gov/Blast.cgi?PAGE=Proteins). A phylogenetic tree constructed by the Neighbor-joining method using 18 CABYV accessions and Potato leafroll virus as an outlier (Fig. 2) showed that the closest accessions to MK671010 and MK671014 were NC003688 (France) and EU636992 (China) with respective nucleotide identity of 98% and 99%. In 2019, another outbreak was observed in the same field near Sadovo and in a field near Plovdiv planted with pumpkins. Nearly 30% of the plants showed leaf yellowing typical for Polerovirus infection. Screening of collected samples (n=17) by RT-PCR confirmed CABYV presence in 15 samples. Based on available reports and according to our knowledge this is the first report of CABYV in Bulgaria.

Intraosseous Epidermoid Cyst: a Case Report.

Background: Epidermoid cysts are benign lesions that occur throughout the body. Their development in the oral cavity is extremely rare. Intraosseous epidermoid cysts of the jaw are even rarer and difficult to distinguish from other lesions. For this reason, we would like to draw the attention of practitioners to this pathology as a differential diagnosis through the presented clinical case. Methods: This study presents an unusual case of a type of epidermoid cyst in an edentulous maxilla. A 70-year-old man was referred to the Maxillofacial Surgery Division at the University Multiprofile Hospital for Active Treatment and Emergency Medicine "N. I. Pirogov", Sofia, Bulgaria, for a single radiolucent area in his anterior maxilla. The patient underwent surgery to extract the cyst. Results: Based on the clinical and radiographic evaluation, a preliminary diagnosis of dentigerous residual cyst was made. The histopathological examination of the hematoxylin and eosin stained sections revealed an epidermoid cyst based on the observed thick keratin layer resembling epidermis together with the stratified squamous epithelium lining with many layers of sheaves of orthokeratin. Conclusions: This report presents an uncommon case of an intraosseous epidermoid cyst occurring without a history of maxillary trauma. Although intraosseous epidermoid cysts are extremely rare in jaws, they should be considered in the differential diagnosis of radiolucent lesions.

New Aspects of Sarcomas of Uterine Corpus-A Brief Narrative Review.

Sarcomas of the uterine corpus are rare malignant neoplasms, which are further classified into mesenchymal tumors, and mixed (epithelial plus mesenchymal) tumors. The main issues concerning these neoplasms are the small number of clinical trials, insufficient data from evidence-based medicine, insignificant interest from the pharmaceutical industry, all of which close a vicious circle. The low frequency of these malignancies implies insufficient experience in the diagnosis, hence incomplete surgical and complex treatment. Additionally, the rarity of these sarcomas makes it very difficult to develop clinical practice guidelines. Preoperative diagnosis, neoadjuvant and adjuvant chemoradiation, target and hormone therapies still raise many controversies. Disagreements about the role and type of surgical treatment are also often observed in medical literature. There are still insufficient data about the role of pelvic lymph node dissection and fertility-sparing surgery. Pathologists' experience is of paramount importance for an accurate diagnosis. Additionally, genetics examinations become part of diagnosis in some sarcomas of the uterine corpus. Some gene mutations observed in uterine sarcomas are associated with different outcomes. Therefore, a development of molecular classification of uterine sarcomas should be considered in the future. In this review, we focus on the epidemiology, pathogenesis, pathology, diagnosis and treatment of the following sarcomas of the uterine corpus: leiomyosarcoma, low- and high-grade endometrial stromal sarcomas, undifferentiated sarcoma and adenosarcoma. Uterine carcinosarcomas are excluded as they represent an epithelial tumor rather than a true sarcoma.

Double Haploid Development and Assessment of Androgenic Competence of Balkan Pepper Core Collection in Bulgaria.

This study was designed to assess the androgenic potential of 180 pepper accessions and 11 progenies (four F1 and seven BC) possessing PMMoV resistance in order to complement an ongoing pepper breeding program. The experiment was carried out in 10 replications with 20 anthers for each accession in two different induction mediums from 2017 to 2019. The highest androgenic response was observed in culture medium 17-2 but differences between two mediums were nonsignificant. From a total of 191 genotypes, 102 genotypes expressed a potential for direct embryogenesis. Embryo induction was seen to be genotype-dependent and decreased in the following order: Pumpkin > Conical > Bell or blocky > Round > Elongate as the most responsive genotypes with over 10% reacted anthers being observed in CAPS-23, CAPS-29, CAPS-127, CAPS-157, CAPS-169, F1 and BC 887 derived from CAPS-23. The number of regenerated plants was higher in the conical group and least in the round varietal group. Regenerated plants were examined visually and by flow cytometry for identification of spontaneous doubled haploids (DH) and haploids. Those originating from F1 and BC progenies were additionally evaluated by a CAPS marker targeting L4 allele for resistance against PMMoV. Obtained results revealed two groups consisting of homozygous susceptible and resistant plants. Therefore, use of anther culture in ongoing breeding will greatly facilitate the pepper genetic improvement.

A step towards Balkan Capsicum annuum L. core collection: Phenotypic and biochemical characterization of 180 accessions for agronomic, fruit quality, and virus resistance traits.

Region-specific local landraces represent a germplasm diversity adapted and acclimatized to local conditions, and are ideal to breed for targeted market niches while maintaining the variability of heirloom traits. A collection of 180 pepper accessions, collected from 62 diverse locations across six Balkan countries, were characterized and evaluated for phenotypic and biochemical variation during a multi-year environment. An assortment of 32 agro-morphological, fruit quality, and virus resistance traits were evaluated, and the top 10% accessions were identified. A wide range of trait variation concerning plant architecture, inflorescence and fruit traits, yield and fruit quality was observed, and appreciable variation was noticed. According to hierarchical clustering, six distinct clusters were established based on pre-defined varietal groups. Divergence among accessions for phenotypic and fruit compositional variability was analyzed, and eight principal components were identified that contributed ~71% of the variation, with fruit shape, width, wall thickness, weight, and fruit quality traits being the most discriminant. Evaluation of the response to tobacco mosaic virus (TMV) and pepper mild mottle mosaic virus (PMMoV) showed that 24 and 1 accession were resistant, respectively while no tomato spotted wilt virus (TSWV) resistance was found. Considerable diversity for agro-bio-morphological traits indicates the Balkan pepper collection as good gene sources for pre-breeding and cultivar development that are locally adapted.

Diffuse Xanthogranulomatous Cholecystitis: Master of Disguise.

A 67-year-old woman presented with clinical symptoms, radiological findings, and preoperative work-up highly suggestive of advanced stage IV carcinoma of the gallbladder (CG). An extended cholecystectomy with the excision of adjacent liver segments and loco-regional lymphadenectomy was performed. Final pathology results revealed diffuse xanthogranulomatous cholecystitis (XG) with ruptured Rokitansky-Aschoff sinuses with tumor-resembling adenomyosis without atypical or malignant cells. There was a reactive inflammatory and fatty degeneration of the adjacent hepatic tissue and a nonspecific inflammatory reaction of the enlarged periportal lymph nodes. The main concern in the management of patients with mass-forming XG is that this benign condition shares strikingly similar clinical, imaging, biochemical, and intraoperative features with advanced CG, which has one of the poorest overall survival rates. Misdiagnosis is not uncommon, which causes significant distress for patients and their families and, in some cases, may result in erroneous treatment. Although the presence of some preoperative imaging findings and/or intraoperative frozen section biopsies may be helpful in suspecting XG, definitive diagnosis is usually delayed until the final pathology result that may come as a surprise. Increasing awareness of this rare, insidious disease will contribute to a better understanding of its biology and natural history and, eventually, help improve management.

Comparative investigation of neuronal nitric oxide synthase immunoreactivity in rat and human claustrum.

We compared the distribution, density and morphological characteristics of nitric oxide synthase-immunoreactive (NOS-ir) neurons in the rat and human claustrum. These neurons were categorized by diameter into three main types: large, medium and small. In the human claustrum, large neurons ranged from 26 to 40µm in diameter, medium neurons from 20 to 25µm and small neurons from 13 to 19µm. In the rat claustrum, large neurons ranged from 19 to 23µm in diameter, medium neurons from 15 to 18µm and small neurons from 10 to 14µm. The cell bodies of large and medium neurons varied broadly in shape - multipolar, elliptical, bipolar and irregular, consistent with a projection neuron phenotype. The small neurons were most seen as being oval or elliptical in shape, resembling an interneuron phenotype. Based on a quantitative comparison of their dendritic characteristics, the NOS-ir neurons of humans and rats displayed a statistically significant difference.

Histologic subtypes of ovarian carcinoma: selected diagnostic and classification problems in Bulgaria: is low hospital volume an issue?

PURPOSE: To provide an overview of the morphologic subtypes of ovarian carcinomas in Bulgaria in relation to current healthcare organization using Bulgarian National Cancer Registry data. Further, we investigated hospital volume as a factor influencing the quality of care for patients with ovarian cancer. METHODS: Bulgarian National Cancer Registry ovarian carcinoma data were retrieved (2009-2011) and distribution of histologic types was analyzed. Cases were divided and compared with respect to main treatment: no surgery, surgery at hospitals dealing with ≥30 ovarian cancer patients/year (high volume), and surgery at hospitals dealing with <30 ovarian cancer patients/year (low volume). We then estimated the odds of being diagnosed with adenocarcinoma and carcinoma not otherwise specified (NOS) vs specified morphologies (serous, endometrioid, clear cell, and mucinous), including age, grade, stage, and hospital volume, in a logistic regression model. RESULTS: A total of 2,041 ovarian carcinomas were distributed as follows: serous 47.7%, mucinous 11.9%, endometrioid 5.8%, clear cell 1.8%, and adenocarcinoma and carcinoma NOS 32.5%. More than half of cancer patients (n = 1,100, 53.9%) were surgically treated in low-volume hospitals and they had a larger proportion of cases with adenocarcinoma and carcinoma NOS: 33.3%, in comparison with 24.0% in high-volume hospitals (p<0.0001). The odds of being diagnosed with unspecified morphology, assumed as a proxy of suboptimal quality of care, are higher for patients surgically treated in low-volume hospitals (odds ratio 1.50 [95% confidence interval 1.21-1.87]) compared with high-volume hospitals after adjustment for age, stage, and grade. CONCLUSIONS: The results of our study may serve policymakers and healthcare professionals when optimizing diagnosis and treatment of ovarian cancer in Bulgaria.

A rare combination between familial multiple lipomatosis and extragastrointestinal stromal tumor.

INTRODUCTION: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Rarely, GISTs can be located in mesentery, retroperitoneal space, omentum or pancreas. In these cases, the neoplasm is defined as "extra-gastrointestinal stromal tumors" (EGISTs). PRESENTATION OF CASE: We reported a case of a 63-year-old male patient diagnosed by computer tomography with large intraabdominal tumor with vague origin, postoperatively determined as an EGIST. The diagnosis was confirmed by immunohistochemical study. The patient had multiple, subcutaneous, painless lipomas localized in the arms, forearms, thighs, abdomen and thorax. Because of the family history and the clinical presentation the disease was determined as familial multiple lipomatosis (FML). We performed radical tumor resection with distal pancreatectomy and splenectomy, and abdominoplasty, removing redundant skin and underlying subcutaneous fat tissue with multiple lipomas. DISCUSSION: FML is a rare hereditary benign disease. On the other hand, only few cases with familial GIST have been reported. In cases with extensive abdominal involvement, the primary origin of EGIST may be impossible to determine so the differential diagnosis is very difficult. CONCLUSION: Although we could not prove correlation between the observed diseases, they are extremely rare and their combination is unusual which makes the presented case valuable and interesting.

The role of small heat-shock protein αB-crystalline (HspB5) in COPD pathogenesis.

BACKGROUND: αB-crystallin (HspB5) is a chaperone whose role as a marker of innate immunity activation as well as its therapeutic potential have recently been investigated in several inflammatory diseases: multiple sclerosis, myocardial ischemia, and Guillain-Barré syndrome. AIM: The aim of this study is to determine the role of αB-crystallin in chronic obstructive pulmonary disease (COPD) pathogenesis and inflammation. MATERIALS: Plasma levels of αB-crystallin were studied in 163 patients: 52 healthy non-COPD smokers; 20 COPD smokers in Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages I-II; 43 COPD smokers in GOLD stages III-IV. Forty-eight patients were diagnosed with acute inflammatory respiratory disease. The plasma levels of αB-crystallin antibodies were determined by an enzyme-linked immunosorbent assay (Calbiochem), and were confirmed with Western blotting. Tissue expression of the protein was compared in three different groups of patients: COPD smokers, COPD nonsmokers, and in patients with age-related emphysema. RESULTS: The mean level of anti-αB-crystallin antibodies in non-COPD smokers was 0.291 nm. In COPD smokers it was 0.352 nm and, in patients with inflammatory lung diseases, 0.433 nm. There was a statistically significant difference between COPD smokers and healthy non-COPD smokers (P = 0.010). The same could be observed comparing the group of patients with acute inflammation and non-COPD healthy smokers (P = 0.007). There was no statistically significant difference between patients with mild/moderate inflammation and those with severe COPD. Tissue detection of the protein showed that it was significantly overexpressed in COPD smokers in comparison to COPD nonsmokers and was only slightly expressed in patients with age-related emphysema. CONCLUSION: αB-crystallin is increased in patients with inflammatory lung diseases. Though unspecific, it could be used in a panel of markers discerning COPD smokers from healthy nonsmokers. As αB-crystallin is a regulator of innate immunity and a therapeutic anti-inflammatory agent, its exact role in COPD pathogenesis and therapy should be explored further.